Transcriptomics analysis reveals new insights in E171-induced molecular alterations in a mouse model of colon cancer

Heloise Proquin; Marlon J. Jetten; Marloes C. M. Jonkhout; Luis Garduno-Balderas; Jacob J. Briede; Theo M. de Kok; Henk van Loveren; Yolanda I. Chirino

doi:10.1038/s41598-018-28063-z

Transcriptomics analysis reveals new insights in E171-induced molecular alterations in a mouse model of colon cancer

Heloise Proquin^*, Marlon J. Jetten, Marloes C. M. Jonkhout, Luis Garduno-Balderas, Jacob J. Briede, Theo M. de Kok, Henk van Loveren, Yolanda I. Chirino

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Titanium dioxide as a food additive (E171) has been demonstrated to facilitate growth of chemically induced colorectal tumours in vivo and induce transcriptomic changes suggestive of an immune system impairment and cancer development. The present study aimed to investigate the molecular mechanisms behind the tumour stimulatory effects of E171 in combination with azoxymethane (AOM)/dextran sodium sulphate (DSS) and compare these results to a recent study performed under the same conditions with E171 only. BALB/c mice underwent exposure to 5 mg/kgbw/day of E171 by gavage for 2, 7, 14, and 21 days. Whole genome mRNA microarray analyses on the distal colon were performed. The results show that E171 induced a downregulation of genes involved in the innate and adaptive immune system, suggesting impairment of this system. In addition, over time, signalling genes involved in colorectal cancer and other types of cancers were modulated. In relation to cancer development, effects potentially associated with oxidative stress were observed through modulation of genes related to antioxidant production. E171 affected genes involved in biotransformation of xenobiotics which can form reactive intermediates resulting in toxicological effects. These transcriptomics data reflect the early biological responses induced by E171 which precede tumour formation in an AOM/DSS mouse model.

Original language	English
Article number	9738
Number of pages	16
Journal	Scientific Reports
Volume	8
DOIs	https://doi.org/10.1038/s41598-018-28063-z
Publication status	Published - 27 Jun 2018

Keywords

TITANIUM-DIOXIDE NANOPARTICLES
PROTEIN-COUPLED RECEPTORS
COLORECTAL-CANCER
OXIDATIVE STRESS
CELL-LINES
CARDIAC FIBROBLASTS
COLLAGEN-SYNTHESIS
UVEAL MELANOMA
FOOD-PRODUCTS
DNA-DAMAGE

Access to Document

10.1038/s41598-018-28063-zLicence: CC BY

Cite this

@article{10c356b570ec493ebebe420ed2c2dd14,

title = "Transcriptomics analysis reveals new insights in E171-induced molecular alterations in a mouse model of colon cancer",

abstract = "Titanium dioxide as a food additive (E171) has been demonstrated to facilitate growth of chemically induced colorectal tumours in vivo and induce transcriptomic changes suggestive of an immune system impairment and cancer development. The present study aimed to investigate the molecular mechanisms behind the tumour stimulatory effects of E171 in combination with azoxymethane (AOM)/dextran sodium sulphate (DSS) and compare these results to a recent study performed under the same conditions with E171 only. BALB/c mice underwent exposure to 5 mg/kgbw/day of E171 by gavage for 2, 7, 14, and 21 days. Whole genome mRNA microarray analyses on the distal colon were performed. The results show that E171 induced a downregulation of genes involved in the innate and adaptive immune system, suggesting impairment of this system. In addition, over time, signalling genes involved in colorectal cancer and other types of cancers were modulated. In relation to cancer development, effects potentially associated with oxidative stress were observed through modulation of genes related to antioxidant production. E171 affected genes involved in biotransformation of xenobiotics which can form reactive intermediates resulting in toxicological effects. These transcriptomics data reflect the early biological responses induced by E171 which precede tumour formation in an AOM/DSS mouse model.",

keywords = "TITANIUM-DIOXIDE NANOPARTICLES, PROTEIN-COUPLED RECEPTORS, COLORECTAL-CANCER, OXIDATIVE STRESS, CELL-LINES, CARDIAC FIBROBLASTS, COLLAGEN-SYNTHESIS, UVEAL MELANOMA, FOOD-PRODUCTS, DNA-DAMAGE",

author = "Heloise Proquin and Jetten, {Marlon J.} and Jonkhout, {Marloes C. M.} and Luis Garduno-Balderas and Briede, {Jacob J.} and {de Kok}, {Theo M.} and {van Loveren}, Henk and Chirino, {Yolanda I.}",

year = "2018",

month = jun,

day = "27",

doi = "10.1038/s41598-018-28063-z",

language = "English",

volume = "8",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Transcriptomics analysis reveals new insights in E171-induced molecular alterations in a mouse model of colon cancer

AU - Proquin, Heloise

AU - Jetten, Marlon J.

AU - Jonkhout, Marloes C. M.

AU - Garduno-Balderas, Luis

AU - Briede, Jacob J.

AU - de Kok, Theo M.

AU - van Loveren, Henk

AU - Chirino, Yolanda I.

PY - 2018/6/27

Y1 - 2018/6/27

N2 - Titanium dioxide as a food additive (E171) has been demonstrated to facilitate growth of chemically induced colorectal tumours in vivo and induce transcriptomic changes suggestive of an immune system impairment and cancer development. The present study aimed to investigate the molecular mechanisms behind the tumour stimulatory effects of E171 in combination with azoxymethane (AOM)/dextran sodium sulphate (DSS) and compare these results to a recent study performed under the same conditions with E171 only. BALB/c mice underwent exposure to 5 mg/kgbw/day of E171 by gavage for 2, 7, 14, and 21 days. Whole genome mRNA microarray analyses on the distal colon were performed. The results show that E171 induced a downregulation of genes involved in the innate and adaptive immune system, suggesting impairment of this system. In addition, over time, signalling genes involved in colorectal cancer and other types of cancers were modulated. In relation to cancer development, effects potentially associated with oxidative stress were observed through modulation of genes related to antioxidant production. E171 affected genes involved in biotransformation of xenobiotics which can form reactive intermediates resulting in toxicological effects. These transcriptomics data reflect the early biological responses induced by E171 which precede tumour formation in an AOM/DSS mouse model.

AB - Titanium dioxide as a food additive (E171) has been demonstrated to facilitate growth of chemically induced colorectal tumours in vivo and induce transcriptomic changes suggestive of an immune system impairment and cancer development. The present study aimed to investigate the molecular mechanisms behind the tumour stimulatory effects of E171 in combination with azoxymethane (AOM)/dextran sodium sulphate (DSS) and compare these results to a recent study performed under the same conditions with E171 only. BALB/c mice underwent exposure to 5 mg/kgbw/day of E171 by gavage for 2, 7, 14, and 21 days. Whole genome mRNA microarray analyses on the distal colon were performed. The results show that E171 induced a downregulation of genes involved in the innate and adaptive immune system, suggesting impairment of this system. In addition, over time, signalling genes involved in colorectal cancer and other types of cancers were modulated. In relation to cancer development, effects potentially associated with oxidative stress were observed through modulation of genes related to antioxidant production. E171 affected genes involved in biotransformation of xenobiotics which can form reactive intermediates resulting in toxicological effects. These transcriptomics data reflect the early biological responses induced by E171 which precede tumour formation in an AOM/DSS mouse model.

KW - TITANIUM-DIOXIDE NANOPARTICLES

KW - PROTEIN-COUPLED RECEPTORS

KW - COLORECTAL-CANCER

KW - OXIDATIVE STRESS

KW - CELL-LINES

KW - CARDIAC FIBROBLASTS

KW - COLLAGEN-SYNTHESIS

KW - UVEAL MELANOMA

KW - FOOD-PRODUCTS

KW - DNA-DAMAGE

U2 - 10.1038/s41598-018-28063-z

DO - 10.1038/s41598-018-28063-z

M3 - Article

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

M1 - 9738

ER -